SEARCH:   Advanced

Blood, 1 July 2006, Vol. 108, No. 1, pp. 38-44. Prepublished online as a Blood First Edition Paper on March 7, 2006; DOI 10.1182/blood-2005-06-2599. This Article Full Text (PDF) All Versions of this Article: 2005-06-2599v1 108/1/38    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhang, N. Articles by Oppenheim, J. J Search for Related Content PubMed PubMed Citation Articles by Zhang, N. Articles by Oppenheim, J. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 30, 2005 Accepted February 20, 2006 Adenosine A2a receptors induce heterologous desensitization of chemokine receptors Ning Zhang, De Yang, Huifang Dong, Qian Chen, Dessislava I Dimitrova, Thomas J Rogers, Michail Sitkovsky, and Joost J Oppenheim* Laboratory of Molecular Immunoregulation, Center for Cancer Research and Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD, USA; Department of Chemical Biology, and State Key Laboratory of Molecular Dynamic and Stable Structures, College of Chemistry, Peking University, Beijing, China Laboratory of Molecular Immunoregulation, Center for Cancer Research and Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD, USA New England Inflammation and Tissue Protection Institute, Northeastern University, Boston, MA, USA Department of Pharmacology, Fels Institute for Cancer Research and Molecular Biology, Center for Substance Abuse Research, Temple University School of Medicine, Philadephia, PA, USA * Corresponding author; email: oppenhei{at}ncifcrf.gov. Adenosine, released by cells in injurious and/or hypoxic environment, possesses potent anti-inflammatory effects by inhibiting the production of pro-inflammatory cytokines and superoxide anions (O2). We hypothesized that adenosine desensitized chemokine receptor-mediated leukocyte trafficking, thus contributing to the anti-inflammatory effects. Our results show that treatment with adenosine or CGS21680, suppressed RANTES-induced chemotaxis and Ca2+ flux by human monocytes, while N6-cyclopentyladenosine (CPA) had no inhibitory effects. ZM241385 blocked the inhibitory effects of CGS21680, suggesting that A2a receptor signals are responsible for the antichemotactic effects of adenosine. CGS21680 induced a decrease in the expression of RANTES binding sites by primary monocytes. Activation of PKA alone was sufficient to dampen RANTES-induced chemotaxis. Moreover, inhibition of PKA reversed the inhibitory effects of CGS21680, suggesting that PKA was necessary for A2a receptor-mediated heterologous desensitization. In a mouse model, prior administration of CGS21680 blocked RANTES-induced recruitment of leukocytes in an air pouch. Moreover, the adenosine A2a receptor-induced cross-desensitization also reduced the susceptibility of monocytes to infection by an R5 strain of HIV-1. Our results suggest that activation of A2a adenosine receptors down-regulates chemokine receptor function, and such receptor cross-talk was based on the simple mechanism of heterologous-desensitization, thus contributing to the anti-inflammatory activity of adenosine. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Greenwell-Wild, N. Vazquez, W. Jin, Z. Rangel, P. J. Munson, and S. M. Wahl Interleukin-27 inhibition of HIV-1 involves an intermediate induction of type I interferon Blood, August 27, 2009; 114(9): 1864 - 1874. [Abstract] [Full Text] [PDF] J. L. Bussiere, P. Martin, M. Horner, J. Couch, M. Flaherty, L. Andrews, J. Beyer, and C. Horvath Alternative Strategies for Toxicity Testing of Species-Specific Biopharmaceuticals International Journal of Toxicology, May 1, 2009; 28(3): 230 - 253. [Abstract] [Full Text] [PDF] S. Kreth, C. Ledderose, I. Kaufmann, G. Groeger, and M. Thiel Differential expression of 5'-UTR splice variants of the adenosine A2A receptor gene in human granulocytes: identification, characterization, and functional impact on activation FASEB J, September 1, 2008; 22(9): 3276 - 3286. [Abstract] [Full Text] [PDF] D. van der Hoeven, T. C. Wan, and J. A. Auchampach Activation of the A3 Adenosine Receptor Suppresses Superoxide Production and Chemotaxis of Mouse Bone Marrow Neutrophils Mol. Pharmacol., September 1, 2008; 74(3): 685 - 696. [Abstract] [Full Text] [PDF] C. Lauro, S. Di Angelantonio, R. Cipriani, F. Sobrero, L. Antonilli, V. Brusadin, D. Ragozzino, and C. Limatola Activity of Adenosine Receptors Type 1 Is Required for CX3CL1-Mediated Neuroprotection and Neuromodulation in Hippocampal Neurons J. Immunol., June 1, 2008; 180(11): 7590 - 7596. [Abstract] [Full Text] [PDF] J. Xu, Y. Chen, R. Lu, C. Cottingham, K. Jiao, and Q. Wang Protein Kinase A Phosphorylation of Spinophilin Modulates Its Interaction with the {alpha}2A-Adrenergic Receptor (AR) and Alters Temporal Properties of {alpha}2AAR Internalization J. Biol. Chem., May 23, 2008; 283(21): 14516 - 14523. [Abstract] [Full Text] [PDF] V. L. Kolachala, R. Bajaj, M. Chalasani, and S. V. Sitaraman Purinergic receptors in gastrointestinal inflammation Am J Physiol Gastrointest Liver Physiol, February 1, 2008; 294(2): G401 - G410. [Abstract] [Full Text] [PDF] B. Rabe, A. Chalaris, U. May, G. H. Waetzig, D. Seegert, A. S. Williams, S. A. Jones, S. Rose-John, and J. Scheller Transgenic blockade of interleukin 6 transsignaling abrogates inflammation Blood, February 1, 2008; 111(3): 1021 - 1028. [Abstract] [Full Text] [PDF] B. Csoka, Z. H. Nemeth, L. Virag, P. Gergely, S. J. Leibovich, P. Pacher, C.-X. Sun, M. R. Blackburn, E. S. Vizi, E. A. Deitch, et al. A2A adenosine receptors and C/EBP{beta} are crucially required for IL-10 production by macrophages exposed to Escherichia coli Blood, October 1, 2007; 110(7): 2685 - 2695. [Abstract] [Full Text] [PDF] S. M. Anderson, M. M. Tomayko, A. Ahuja, A. M. Haberman, and M. J. Shlomchik New markers for murine memory B cells that define mutated and unmutated subsets J. Exp. Med., September 3, 2007; 204(9): 2103 - 2114. [Abstract] [Full Text] [PDF] C. De Ponti, R. Carini, E. Alchera, M. P. Nitti, M. Locati, E. Albano, G. Cairo, and L. Tacchini Adenosine A2a receptor-mediated, normoxic induction of HIF-1 through PKC and PI-3K-dependent pathways in macrophages J. Leukoc. Biol., August 1, 2007; 82(2): 392 - 402. [Abstract] [Full Text] [PDF] J. Reutershan, R. E. Cagnina, D. Chang, J. Linden, and K. Ley Therapeutic Anti-Inflammatory Effects of Myeloid Cell Adenosine Receptor A2a Stimulation in Lipopolysaccharide-Induced Lung Injury J. Immunol., July 15, 2007; 179(2): 1254 - 1263. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020